MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal
MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal
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DOI：
10.1002/stem.2830
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发表时间：
2018-08-01
期刊：
影响因子：
5.2
通讯作者：
Vardy, Leah A.
中科院分区：
文献类型：
--
作者：
James, Christina;Zhao, Tian Yun;Vardy, Leah A.
胚胎干细胞具有自我更新或分化的能力，并且这些过程受到严格控制。我们之前报道过多胺调节因子 AMD1 对于胚胎干细胞的自我更新至关重要。多胺腐胺、亚精胺和精胺是重要的有机阳离子，在多种细胞过程中发挥作用。在这里，我们探讨了多胺在促进自我更新中的重要作用，并确定了一种作用于多胺下游的新干细胞调节因子：MINDY1。 MINDY1 蛋白水平在胚胎干细胞 (ESC) 中很高，并且依赖于高多胺水平。在缺乏通常必需的细胞因子白血病抑制因子 (LIF) 的情况下，MINDY1 的过度表达可以促进 ESC 自我更新。 MINDY1 蛋白被异戊二烯化，这种修饰对于其促进自我更新的能力是必需的。我们继续证明 Mindy1 RNA 在神经前体细胞分化过程中被 mir-710 抑制。总而言之，这些数据表明 ESC 自我更新需要高水平的多胺，并且它们在一定程度上通过促进高 MINDY1 水平发挥作用。
Embryonic stem cells have the ability to self-renew or differentiate and these processes are under tight control. We previously reported that the polyamine regulator AMD1 is critical for embryonic stem cell self-renewal. The polyamines putrescine, spermidine, and spermine are essential organic cations that play a role in a wide array of cellular processes. Here, we explore the essential role of the polyamines in the promotion of self-renewal and identify a new stem cell regulator that acts downstream of the polyamines: MINDY1. MINDY1 protein levels are high in embryonic stem cells (ESCs) and are dependent on high polyamine levels. Overexpression of MINDY1 can promote ESC self-renewal in the absence of the usually essential cytokine Leukemia Inhibitory Factor (LIF). MINDY1 protein is prenylated and this modification is required for its ability to promote self-renewal. We go on to show that Mindy1 RNA is targeted for repression by mir-710 during Neural Precursor cell differentiation. Taken together, these data demonstrate that high polyamine levels are required for ESC self-renewal and that they function, in part, through promotion of high MINDY1 levels.